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Since dehydroepiandrosterone (DHEA) was discovered in 1934, scientists have been probing its metabolism, endocrinologists have been studying its functions, doctors have been debating its uses and abuses, and the supplement industry has been touting its virtues. It's a confusing mix of science, speculation, and commerce. What is the status of this controversial chemical?
What is it?
DHEA is a steroid hormone. Like cortisol and the sex hormones, it's produced by the body, with cholesterol as its main building block. Most of that production occurs in the adrenal glands, small structures that sit on top of the kidneys at the rear of the abdomen. Lesser amounts are also manufactured in the intestinal tract and brain. Most of the DHEA in the bloodstream circulates in the form of a derivative, DHEA sulfate (DHEAS). The intestines also convert DHEA supplements into DHEAS before the hormone enters the blood. Since DHEA and DHEAS are so closely related and can be converted into each other by the body, it's reasonable to consider them together as DHEA.
By any name, DHEA is a weak androgen, or male hormone. The body converts most of its DHEA into androstenedione; yes, it's the very same androgen made famous by Mark McGwire during his epic home-run season. But the metabolism of DHEA does not stop with "andro"; instead, the body converts it to a wide array of androgens and estrogens, including the male hormone testosterone and the female hormone estradiol.
DHEA and aging
Perhaps the most important reason that DHEA has attracted so much attention is its dramatic and puzzling relationship to aging. DHEA production begins during fetal life; in fact, fetal adrenal glands manufacture more than 200 mg daily, nearly 10 times more than the amount adults produce. After birth, though, DHEA production slows to a crawl, and blood levels are very low. That changes about the time of puberty, when levels begin to rise again. In both men and women, DHEA levels peak between age 20 and 30, after which they decline steadily by about 5% a year. At its peak in young men, DHEA achieves blood levels 10 times higher than any other steroid hormone, molecule for molecule. But by the age of 70, it has declined to very low, nearly negligible levels.
Men don't know whether their DHEA levels are sky high or bargain basement low, but they certainly know they're getting older. As the clock ticks, men lose muscle mass and strength. Bone density declines, often leading to osteoporosis and, on average, a loss of about 2 inches of height. Fat begins to accumulate around the midsection, and heart disease, high blood pressure, and diabetes become progressively more common. And over time, sexual desire tends to wane and many men develop erectile dysfunction.
DHEA has been touted as the "anti-aging hormone," because the effects of aging develop as the level of DHEA falls. But does this decline actually contribute to the changes of aging, or is DHEA merely a fellow traveler, drifting down as part of the normal aging process without affecting it one way or another? It's a basic question. If DHEA has a role in aging, supplements might be helpful, but if it doesn't, supplements would be useless at best.
Why is it there?
Scientists understand DHEA's chemical structure and know about its metabolism and its ebb and flow during the life cycle. But they don't really understand its function in health or its possible contribution to disease. Hundreds of studies have been published, but many are flawed or incomplete. And trials of DHEA therapy are just as confusing: The preparations, doses, and duration of treatment vary; the standards used to evaluate benefits differ; and testing for side effects is inconsistent.
Given these difficulties, it's not surprising that the research results are often contradictory. But since advocates and critics often pick and choose to construct their sound bites, you should know something about the range of reports. Here's a brief summary of some recent investigations — but don't stock up on DHEA until you've read about the best studies, at the end.
Body fat
Perhaps the most optimistic study of DHEA was published in 2004. Scientists from the Washington University School of Medicine in St. Louis evaluated 56 healthy men and women between the ages of 65 and 78. Half the volunteers were randomly assigned to receive 50 mg of DHEA a day while the others got a placebo. At the end of six months, the DHEA group lost only a few pounds, but most of it was the most harmful kind, abdominal fat; in men, it amounted to a loss of about 7% of their abdominal fat. In addition, the DHEA group displayed an improved sensitivity to insulin. No side effects were recorded. Testosterone and PSA levels did not change during the trial, but estradiol and insulin-like growth factor-1 (IGF-1) levels rose in both men and women.
It would be nice if a simple, safe supplement could reduce abdominal fat and improve insulin's action. But the Washington University report cites three earlier studies that reached different conclusions. More study is needed — as it is for most questions about DHEA.
Muscle and bone
Androgens exert a powerful influence on body composition. Among other things, they help explain why men have more muscle mass and a higher bone mineral density than women. These advantages diminish with age. Above age 40, testosterone levels drift down by just 1% a year, but DHEA levels plummet. Perhaps DHEA supplements can keep muscles and bones youthful as men age.
To date, unfortunately, the results have not been encouraging. American scientists evaluated 43 healthy men between 55 and 80; they were randomly assigned to receive 90 mg of DHEA a day or a placebo. At the end of six months, the hormone had not shown any ability to build stronger bones. Similarly, a French study of 140 men and 140 women between 60 and 80 found that 50 mg of DHEA failed to increase muscle mass, muscle strength, or to decrease muscle fat during one year of supplementation.
Coronary artery disease
It's the leading cause of death in American men, and its prevalence rises with age, just as DHEA levels decline. But does that mean DHEA can help?
Animal studies and laboratory research are contradictory. In some experiments, DHEA appears to slow the formation of cholesterol-laden plaques in the arteries of animals fed high-fat diets. But in a lab experiment, the hormone accelerated the transformation of human macrophages into foam cells, the very cells that accumulate in plaques.
Clinical studies are no less confusing. In the Massachusetts Male Aging Study, for example, men with the lowest DHEA levels had the highest risk of heart disease — but in the Massachusetts Women's Health Study, high DHEA levels were linked to increased risk. That might suggest that what's bad for the goose is good for the gander. But in the case of DHEA, nothing is that simple. A 12-week Japanese study of 24 men reported that DHEA can improve endothelial function; that might reduce the risk of heart attacks and strokes, but a 19-year study of 1,029 men and 942 women reported no link between DHEA levels and the risk of coronary artery disease.
Confused about DHEA and cardiovascular disease? Take heart; scientists are confused, too.
Cognitive function
Wisdom is one of the few positive attributes of aging — or, at least, it should be. In fact, about 7% of Americans develop cognitive impairment by the age of 65, and by 85, the number is up to 40%. It's no wonder that Alzheimer's disease and other forms of dementia are among the most dreaded complications of aging.
"Improved memory" is one of the major reasons people purchase DHEA. Are they getting their money's worth? The Baltimore Longitudinal Study of Aging is not optimistic. When scientists tracked 883 men for up to 31 years, they did not detect any relationship between cognitive status or cognitive decline and DHEA levels. And a six-month randomized clinical trial of 100 mg of DHEA a day in 58 patients with Alzheimer's disease did not detect any improvement in cognitive performance or the severity of the disease.
Depression
The effects of DHEA on cognitive function are depressing, but trials of DHEA for depression are more encouraging. A 1999 study of patients with major depression compared the results of 90 mg of DHEA a day with those of a placebo; at the end of the six weeks, 5 of the 11 patients who received DHEA improved, but none of the 11 who received a placebo did. A 2005 study used 90 mg a day for three weeks followed by the very high dose of 450 mg a day for three weeks. At the end of six weeks, 6 of 14 DHEA patients had improved compared with 1 of the 15 placebo recipients.
It's a ray of hope for DHEA. But larger and longer studies are needed. It will also be important to compare DHEA with other supplements, such as St. John's wort, prescription medications, and talk therapies.
Well-being and sexuality
If DHEA won't make you think better, might it at least make you feel better? Several trials have reported improved energy and overall feelings of well-being, but most are small or short-term studies that use only nonvalidated personal interviews to assess benefit. In contrast, a well-controlled one-year trial of 50 mg of DHEA a day in 280 volunteers did not detect improved psychological or general well-being. Libido was enhanced in older women but not men. Although several studies have linked low levels of DHEA to erectile dysfunction, none has demonstrated that supplements improve sexual performance in men.
Adrenal replacement therapy
At present, there is only one fairly well established medical indication for DHEA therapy. Adrenal insufficiency is an uncommon condition in which the adrenal glands fail to produce sufficient amounts of steroid hormones. Standard therapy involves replacing the two major categories of these hormones, glucocorticoids (such as hydrocortisone) and mineralocorticoids (such as fluorocortisol). These hormones are life-saving, but several studies have reported that additional therapy with DHEA results in further improvements in mood and well-being as well as enhanced sexual function in women.
Overall effects
Careful clinical studies of DHEA's overall impact are badly needed, and two major investigations represent a giant step in that direction. Scientists at the University of Missouri School of Medicine studied 39 men between 60 and 84; because all were part of the ongoing Longitudinal Aging Study, the researchers were able to evaluate DHEA against a backdrop of careful clinical measurements over nearly 30 years.
All the volunteers were in good health when the nine-month DHEA trial began. The men were randomly assigned to take either DHEA or a placebo; neither the participants nor the researchers knew which men were taking the hormone and which the placebo. The DHEA dose was 100 mg a day, a typical "replacement dose" calculated to boost DHEA blood levels into the youthful range.
Each man underwent careful evaluations before and after treatment. When the results were tallied, the researchers found no evidence that DHEA had any benefits. The men who took the hormone did not exhibit either a decrease in body fat or an increase in muscle mass; body weight did not change appreciably. Insulin and blood sugar levels were also unchanged. DHEA failed to produce an improvement in sexual function; similarly, there were no changes in overall subjective well-being. Hormone therapy was associated with small alterations in red blood cell counts, cholesterol levels, and kidney function tests, but all of these results remained within the normal range.
The Missouri scientists also checked for potential adverse effects, but they detected none. In particular, PSA levels did not rise, and urinary function did not change.
All in all, DHEA produced little change for good or ill. Both proponents and critics of the hormone might argue that the dose was simply too small, but the researchers measured blood levels and found that DHEA levels increased dramatically during the trial; DHEA itself more than doubled, and DHEAS increased more than fivefold. As further evidence of a hormonal effect, the scientists reported that DHEA therapy produced a sharp increase in both male (free testosterone) and female (estradiol) hormone levels.
A 2006 study from the Mayo Clinic reported similar findings. The subjects included 87 men between 62 and 73; all the men had low levels of DHEA and testosterone when the trial began. The men were randomly assigned to receive either DHEA (75 mg a day), testosterone (5 mg a day), or a placebo. At the end of two years, neither DHEA nor testosterone produced any beneficial effects in body composition, physical performance, insulin sensitivity, or quality of life. A parallel trial of DHEA in 57 elderly women was equally disappointing.
Side effects
Because DHEA is an androgen, it has the potential for causing the side effects associated with male hormones. These include the growth of facial hair and the loss of scalp hair, acne, deepening of the voice, breast swelling in men, rising blood pressure, and declining HDL ("good") cholesterol. Fortunately, the published trials of DHEA do not report these side effects in men. Another long-term worry for men is enlargement of the prostate and an increased risk of prostate cancer. It's reassuring that the DHEA trials do not report PSA elevations, but these are all short-term studies. Several trials do note a rise in IGF-1 levels. It's a concern, since researchers from Harvard were the first to implicate IGF-1 as a prostate cancer risk factor.
Hope or hype? Drug or nutrient?
DHEA is big business, reaping tens of millions of dollars for the supplement industry each year. It is heavily promoted as a "super hormone" and an "antidote for aging" that can strengthen the immune system, slow memory loss, melt body fat, build strong muscles and bones, prevent heart disease and cancer, enhance energy and sexuality, and fight Alzheimer's disease.
None of these claims is supported by current medical science. But that has not stopped manufacturers from touting the hormone. It wasn't always that way. When the DHEA craze began in 1985, the FDA banned over-the-counter sales of the drug. DHEA is still outlawed by the International Olympic Committee and the National Collegiate Athletic Association, but the FDA has fallen silent. That's because Congress passed the Dietary Supplement Health and Education Act in 1994, removing nutritional supplements from the jurisdiction of the FDA. In a matter of months, DHEA was back, this time as a "nutrient." Still, if you hunt for it in a market, you'll find it with medications, not carrots.
DHEA is controversial. Despite the heated debate, two facts about DHEA are incontrovertible: It is a hormone, and it is not part of the human diet. Since DHEA is available without a prescription, it's up to each man to decide if it's right for him. The same is true for all supplements, and in considering any of them, men should use common sense and caution. Remember that supplements are not subject to FDA standards of purity, potency, efficacy, and safety. And neither booming sales nor gushing testimonials prove that a product is really effective, and "all-natural" origins do not prove that a substance is safe.
More research on DHEA is needed to learn its normal function as well as to determine the possible value of supplements. For now, men would be wise to consider two ancient dictums, one from medicine, and the other from the marketplace: Primum non nocere (first, do no harm) and caveat emptor (buyer beware).